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XYLESTESIN WITH ADRENALINE 20 MG/ML + 12.5 MICROGRAMS/ML SOLUTION FOR INJECTION

Active substance(s): EPINEPHRINE / LIDOCAINE HYDROCHLORIDE

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Xylestesin
with Adrenaline
20 mg/ml + 12.5
micrograms/ml
solution for
injection


Lidocaine hydrochloride/
Adrenaline (epinephrine)

Read all of this leaflet carefully before you start using this
medicine because it contains important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, dentist or
pharmacist.
- If you get any side effects talk to your doctor, dentist or pharmacist.
This includes any possible side effects not listed in this leaflet.
See section 4.
What is in this leaflet:
1. What Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml
is and what it is used for
2. What you need to know before you use this medicine
3. How to use this medicine
4. Possible side effects
5. How to store this medicine
6. Contents of the pack and other information
1. WHAT XYLESTESIN™ WITH ADRENALINE 20 MG/ML +
12.5 MICROGRAMS/ML IS AND WHAT IT IS USED FOR
Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml contains the
active substances lidocaine hydrochloride and adrenaline (epinephrine).
This medicine is a local anaesthetic (agent which reduces or abolishes
sensation, affecting a particular region). This medicine is used for local
anaesthesia (loss of feeling or sensation in a part of the body) in dentistry.
This medicine is used in adults, children and adolescents.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE XYLESTESIN™ WITH
ADRENALINE 20 MG/ML + 12.5 MICROGRAMS/ML
Do not use this medicine
• if you are allergic to lidocaine hydrochloride, adrenaline (epinephrine)
sodium sulfite, or any of the other ingredients of this medicine (listed in
section 6) or to local anaesthetics of the amide type
• if you have an impairment of the cardiovascular system in particular:
disturbance of heart rhythm (arrhythmia),
unstable angina pectoris (e.g. severe chest-pain),
recent heart attack (heart infarction),
recent heart surgery,
severe forms of low or high blood pressure
acute heart failure
• if you have any blood disorders known as haemorrhagic diatheses
• if you have an inflammation at the site where the injection is to be given
• if you have recently been given or are taking monoamine oxidase (MAO)
inhibitors or tricyclic antidepressants (medicines for treating depression)
• if you have severe bronchial asthma
• This medicine must not be used at the end of extremities
Warnings and precautions
Talk to your doctor, dentist or pharmacist before using this medicine
• if you have any lung disorders particularly allergic asthma
• if you have any liver or kidney problems
• if you have angina pectoris
• if you have hardening of the arteries
• if you have any thyroid problems
• if you have diabetes mellitus
• if you have any blood disorders including a tendency to bleed or bruise easily
• if you have an eye condition known as narrow-angle glaucoma
• if you have pheochromocytoma (a form of cancer that effects the adrenal
gland)
• if you have impaired cardiovascular function
• if you have a history of epilepsy
• if you have any blood disorders known as methaemoglobinaemia
• There is a possibility that this medicine may show up as positive in routine
blood screening tests on athletes.
Other medicines and Xylestesin™ with Adrenaline 20 mg/ml +
12.5 micrograms/ml
Tell your doctor, dentist or pharmacist if you are taking, have recently taken or
might take any other medicines.
• Monoamine oxidase (MAO) inhibitors or tricyclic antidepressants (drugs
for treating depression), as the cardiovascular impact of this medicine
(e.g. increased blood pressure) might be intensified
• Phenothiazines (medicines for treating severe mental disorders) might
cause a drop in blood pressure, if this medicine is applied simultaneously;
particular caution is advised in case of preexisting low blood pressure
• Non-selective beta-blockers (medicines for treating high blood pressure),
as the simultaneous application of this medicine might cause an increased
blood pressure
• Inhalational anaesthetics (chemical compound possessing general
anaesthetic properties that can be delivered via inhalation) like halothane
may induce irregular heart rhythm (arrhythmia) following administration
of this medicine
• Vasopressor drugs (medicines used to elevate blood pressure) and ergot type
oxytocic drugs (medicines used to induce labour in pregnant women) as the
concomitant use of this medicine may cause severe, prolonged increased
blood pressure
• Local anaesthetics (agent which reduces or abolishes sensation, affecting
a particular region) as a concurrently use with this medicine may additive
negative effects like adverse drug reaction of local anaesthetics.
• Oral antidiabetics (drugs for treating diabetes mellitus), as this medicine
might weaken their effects; if necessary, the dose has to be increased for
avoiding excessive blood glucose levels
Children:
There is no significant different effect expected between adults and children
when taking other medicines in conjunction with this medicine.
Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml with food
Do not eat until the anaesthesia is totally worn off and normal function returns
to avoid inadvertent trauma to the lips, tongue, cheek mucosa or soft palate.
Pregnancy
Caution should be exercised when this medicine is administered to pregnant
women. Therefore ask your doctor or dentist for advice before taking this

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PACKAGE LEAFLET:
INFORMATION FOR THE PATIENT

44000763522/02

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The following information is intended for medical
or healthcare professionals only:

SUMMARY OF PRODUCT
CHARACTERISTICS

Xylestesin
with Adrenaline
20 mg/ml + 12.5
micrograms/ml
solution for
injection


Lidocaine hydrochloride/
Adrenaline (epinephrine)
1 NAME OF THE MEDICINAL PRODUCT
Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml
solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml solution
1 cartridge with
for injection
1.7 ml solution for
contains
injection contains
Lidocaine hydrochloride
20 mg
34 mg
Adrenaline (Epinephrine)
12.5 micrograms 21.25 micrograms
(1:80,000)
(1:80,000)
Excipients of known effect
Sodium sulphite (E221)
0.6 mg
1.02 mg
Sodium*
1.71 mg
2.91 mg
* Sodium content of sodium sulphite and sodium chloride

For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Solution for injection
The solution is a clear, not opalescent, colourless liquid with a pH
value of 3.6 to 4.4.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Local anaesthesia (infiltration and nerve-block anaesthesia) in
dentistry.
This medicine is indicated in adults, adolescents and children aged
more than 4 years.
4.2 Posology and method of administration
This medicine is exclusively recommended for use in dentistry.

Posology
The smallest possible volume of solution which will lead to an
effective anaesthesia should be used.

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Adults:
The dosage should be individually determined from case to case depending
on the method used and special characteristics of the particular case.
In oral infiltration and/or mandibular block, initial dosages of 1.0-4.0 ml
are usually sufficient.
Special populations:
Elderly population: Increased plasma levels of this medicine can occur
in older patients due to diminished metabolic processes and reduced
distribution volume. The risk of accumulation of Xylestesin with Adrenaline
is increased after repeated administration in particular.
Dosages should be reduced from adult recommendations, taking into
consideration any cardiac or liver disease (see section 4.4).

Patients with hepatic impairment: Lidocaine is metabolized by the liver.
Lower doses of lidocaine may be required in patients with hepatic dysfunction due to prolonged effects and systemic accumulation (see section 4.4).
Patients with renal impairment: Lidocaine and its metabolites are mainly
eliminated in urine. Lower doses of lidocaine may be required in patients
with severe renal dysfunction due to prolonged effects and systemic
accumulation (see section 4.4).
Other relevant special populations: The dose has to be likewise reduced in
patients with certain pre-existing diseases (angina pectoris, arteriosclerosis,
see section 4.3 and 4.4) and patients taking contemporary medications
known to interact with lidocaine and/or see section 4.4 and 4.5).
Dose recommendation for special populations: A lower dosage range is
thus recommended in all such cases (i.e. minimum volume of this medicine
for sufficient anaesthetic effect).
Paediatric population:
This medicine is indicated in adults, adolescents and children aged more
than 4 years. Special care has to be exercised when treating children below
4 years. The quantity to be injected should be determined by the age and
weight of the child and the magnitude of the operation. The anaesthesia
technique should be selected carefully. Painful anaesthesia techniques
should be avoided. The behaviour of the child during treatment has to be
monitored carefully. The average dose to be used is in the range of 20 mg
to 30 mg lidocaine hydrochloride per session. The dose in mg of lidocaine
hydrochloride which can be administered in children may alternatively be
calculated from the expression: child’s weight (in kilograms) x 1.33.
The quantity to be injected should be determined by the age and weight of
the child and the magnitude of the operation.
Dose recommendation for children:
Body weight (kg)

Recommended dosage
lidocaine hydrochloride/
mg/child

20-<30
30-<40
40-<45

5-20
10-40

anaesthetic/ml/child
0.25 ml-1 ml
0.5 ml-2 ml

Due to the fact that lidocaine diffuses rapidly into tissues and the density
of bones is lower in children compared to adults, infiltration anaesthesia
instead of conduction anaesthesia can be preferred in paediatric population.
Maximum Recommended Dosage:

Adults:
For healthy adults, the maximum dose of the active ingredient lidocaine
hydrochloride with vasoconstrictor admixture is 7 mg/kg body weight.
Example: The maximum dose for a 70 kg patient is 500 mg. However, due
to the addition of epinephrine 12.5 µg/ml, the maximum administered
quantity of 16 ml solution for injection or 9 cartridges (equivalent to 0.2 mg
epinephrine, maximum dose) must not be exceeded.
Children:
The quantity to be injected should be determined by the age and weight of
the child and the magnitude of the operation. Do not exceed the equivalent
of 5 mg lidocaine hydrochloride/kg bodyweight or 0.250 ml this medicine/kg
bodyweight.

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4.4 Special warnings and precautions for use

Maximum recommended dosage of this medicine in children:
Body weight (kg)
Maximum
(Corresponding paediatric
allowed dose based on 5 mg/kg BW
age groups according to
anaesthetic
± limits of growth tables) Lidocaine hydrochloride
mg/child
ml/child
20-<30

100

5

30-<40

150

7.5

40-<45

200

10.0

45-<50

225

11.3

50-<60

250

12.5

60-<70

300

15.0

70-<80

350

16.0

Method of administration
Dental use
To avoid intravascular injection, aspiration control at least in two planes
(rotation of the needle by 180°) must always be carefully undertaken,
although a negative aspiration result does not safely rule out an unintentional and unnoticed intravascular injection.
The injection rate should not exceed 0.5 ml in 15 seconds, i.e.1 cartridge
per minute.
Major systemic reactions as a result of accidental intravascular injection
can be avoided in most cases by an injection technique - after aspiration
slow injection of 0.1-0.2 ml and slow application of the rest - not earlier
than 20-30 seconds later.
Opened cartridges must not be used in other patients. Residues must be
discarded (see section 6.6).
4.3 Contraindications
This medicine must not be used in
- patients with (a history of) hypersensitivity to the active substances,
sodium sulphite (E221) or to any of the other excipients,
- patients with haemorrhagic diatheses - increased bleeding risk
particularly with nerve-block anaesthesia.
Due to the active substance lidocaine, this medicine must not be used in
the event of
- known allergy or hypersensitivity to local anaesthetics of the amide type,
- severe, uncontrolled or untreated excitation and conduction disorders of
the heart (e.g. grade II and III AV block, pronounced bradycardia),
- acutely decompensated heart failure,
- severe hypotension,
- injection into an inflamed area because of treatment failure due to
reduced penetration of lidocaine into the inflamed area.
Due to the content of epinephrine as a vasoconstrictor admixture,
this medicine must not be used in the event of
- Heart diseases such as:
- unstable angina pectoris,
- recent myocardial infarction,
- recent coronary artery bypass surgery,
- refractory arrhythmias and paroxysmal tachycardia or high-frequency,
continuous arrhythmia,
- untreated or uncontrolled severe hypertension,
- untreated or uncontrolled congestive heart failure,
- concomitant treatment with monoamine oxidase (MAO) inhibitors or
tricyclic antidepressants (see section 4.5).
- This medicine is not allowed to be used in acra of extremities
Due to the content of sulphite as excipient, this medicine is not allowed
to be used in the event of
- allergy or hypersensitivity to sulphite,
- severe bronchial asthma.
This medicine can provoke acute allergic reactions with anaphylactic
symptoms (e.g. bronchospasm).

Special warnings
This medicine must be used with particular caution in the event of
- severe impairment to the renal function,
- angina pectoris (see section 4.2 and 4.3),
- arteriosclerosis,
- considerably impaired blood coagulation or anticoagulatory treatment,
- uncontrolled or untreated hyperthyroidism,
- narrow-angle glaucoma,
- diabetes mellitus,
- lung diseases - particularly allergic asthma bronchiale,
- pheochromocytoma,
- methemoglobinemia.
Dental practitioner who employ local anaesthetic agents should be well
versed in diagnosis and management of emergencies which may arise from
their uses.
Inadvertent intravascular application must be avoided (see section 4.2).
Accidental intravascular injection or accidental overdose may be associated
with convulsions, followed by central nervous system depression or cardiorespiratory arrest (see section 4.9). Resuscitative equipment, oxygen, and
other resuscitative drugs should be available for immediate use.
The product should be administered with caution in patients with impaired
cardiovascular function since they may be less able to compensate for
functional changes associated with the prolongation of A-V conduction
which might be caused by these drugs.
Since amide-type local anaesthetics are also metabolised by the liver, this
medicine should be used with caution in patients with hepatic diseases.
Patients with severe hepatic diseases are at greater risk of developing
toxic plasma concentration.
The product should be administered with caution to patients with history
of epilepsy, particularly high doses should be avoided.
The lower blood flow in the pulp tissue due to the content of epinephrine
and thus the risk to overlook an opened pulp has to be taken into account
regarding cavity or crown preparations.
There is a possibility of positive results on doping tests performed on
sportsmen. Lidocaine is not listed on the current WADA list, and the listed
epinephrine is not forbidden if used as vasoconstrictor in local anaesthetics.
In patients taking anticoagulants or platelet aggregation inhibitors (e.g.
heparin or acetylsalicylic acid) the overall risk of bleeding is increased.
An inadvertent vasopuncture when administering the local anaesthetic can
lead to serious bleeding.
This medicinal product contains less than 1 mmol (23 mg) sodium per 1.7 ml
i.e. essentially “sodium free”.
E221 sodium sulphite: May rarely cause severe hypersensitivity reactions
and bronchospasm.
Information to the patients: The patient should be advised to exert caution
to avoid inadvertent trauma to the lips, tongue, cheek mucosae or soft
palate when these structures are anesthetized. The ingestion of food should
therefore be postponed until normal function returns.
Precautions for use:
Each time a local anaesthetic is used the following medicinal products/
therapy as well as an indwelling i.v. catheter set should be available:
- Anti-convulsant medicines (benzodiazepines e.g. diazepam),
myorelaxants, glucocorticoids, atropine and vasopressors or adrenaline
as well as an electrolyte solution for a severe allergic or anaphylactic
reaction.
- Resuscitating equipment (in particular a source of oxygen) enabling
artificial ventilation if necessary.
- Careful and constant monitoring of cardiovascular and respiratory
(adequacy of ventilation) vital signs and the patient’s state of consciousness should be monitored after each local anaesthetic injection. Restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression,
or drowsiness may be early warning signs of central nervous system
toxicity (see section 4.9).

4.5 Interaction with other medicinal products and other forms
of interaction
Interactions affecting the use of this medicinal product:
• Contraindicated combinations:
Patients taking MAO inhibitors or tricyclic antidepressants
The sympathomimetic effect of epinephrine can be intensified by the
simultaneous intake of MAO inhibitors or tricyclic antidepressants
(see also section 4.3).
• Concomitant use is not recommended:
Patients taking phenothiazines
Phenothiazines may reduce or reverse the pressor effect of epinephrine.
Concurrent use of these agents should generally be avoided.
In situations when concurrent therapy is necessary, careful patient
monitoring is essential.
Patients taking non-selective beta-blockers
The concomitant administration of non-cardioselective β-blockers
can lead to an increase in blood pressure due to the epinephrine in
this medicine.
Inhalational anaesthestics
Certain inhalational anaesthetics, such as halothane, can sensitise the
heart to catecholamines and therefore induce arrhythmias following
administration of this medicine.
Vasopressor and ergot-type oxytocic drugs
Lidocaine hydrochloride with epinephrine 1:80,000 or other vasopressors should not be used concomitantly with ergot-type oxytocic
drugs, because a severe persistent hypertension may occur.
• Precaution including dose adjustment:
Local anaesthetics
Caution is advised if lidocaine with epinephrine is used concurrently
with other local anaesthetics. The toxic effects of local anaesthetics
are additive. A major cause of adverse reactions appears to be
excessive plasma concentrations, which may be due to accidental
intravasal administration, slow metabolic degradation or overdosing.
Interactions resulting in clinically relevant changes on the use of other
medicinal products:
• Concomitant use is not recommended:
Patients taking oral antidiabetics
Epinephrine can inhibit insulin release in the pancreas and thus
diminish the effect of oral antidiabetics.

Fertility
In animal studies no effects on fertility were seen (see section 5.3).
4.7 Effects on the ability to drive and use machines
Although test patients have shown no impairment of their normal reactions
when driving a vehicle, the dentist has to assess in each case the possible
impairment of safety when operating a motor vehicle or machinery. The
patient should not leave the dental office earlier than 30 minutes after the
injection.
4.8 Undesirable effects
a) Summary of the safety profile:
In general, the therapeutic use of this medicine can be regarded as very
safe. The causality assessment in case of adverse events is difficult,
because either the underlying dental disease or the dental procedure or
the local anaesthetic may be the reason of an adverse event, and an
explicit differentiation is not possible. The description of the safety profile
of this medicine is based on data identified in published clinical studies
and on the postmarketing surveillance data of the MAH.
In clinical studies, the most frequently observed adverse events were
hypoaesthesia oral (74%), followed by drug ineffective (8.5%) as well as
pain, procedural pain, toothache (0.25-1.26%). Nerve disturbances were in
clinical studies with exception of hypoaesthesia oral not observed, which
may be explained by the low patient number. Postmarketing surveillance
data confirm the pattern described in published clinical studies in general,
but indicated a lower overall incidence of adverse events. However it has to
be considered that spontaneous reporting systems did not allow incidence
calculation.
The overall risk of nerve disturbances (e.g. hypoaesthesia, paraesthesia,
taste disorders) is low according to the postmarketing experience. In the
case of suspected hypersensitivity reactions, allergy testing is recommended
including testing of the single components of the medicinal product.
b) Tabulated summary of adverse reactions:
The tabulated summary is based on data from published controlled clinical
studies (N = 1,990 patients) and completed by postmarketing data (5-yearsinterval):

Very common (>1/10)
Common (≥ 1/100, <1/10)
Uncommon (≥ 1/1’000, <1/100)
Rare (≥ 1/10’000, <1/1’000)
Very rare (<1/10’000)
Not known (cannot be estimated from the available data)

Paediatric population
No significant differences can be expected regarding drug interactions
between adult and paediatric population.

System organ class

4.6 Fertility, pregnancy and lactation

Infections and infestations

Uncommon
Oral herpes

Immune system disorders

Not known*
anaphylactic reaction, anaphylactic
shock, type I hypersensitivity

Psychiatric disorders

Not known*
confusional state

Nervous system disorders

Uncommon
dizziness

Pregnancy
For this medicine no clinical data on exposed pregnancies are available.
Lidocaine animal studies do not indicate direct or indirect harmful effects
with respect to reproductive toxicity at doses 6.6 times the human dose
(see section 5.3). Animal studies carried out with epinephrine have shown
reproductive toxicity (see section 5.3). The potential risk for humans is
unknown.
Caution should be exercised when prescribing to pregnant women. This
medicine should be used during pregnancy only if the potential benefit
justifies the potential risk to the foetus.
Breast-feeding
Lidocaine is excreted in breast milk with a milk:plasma ratio of 0.4.
No information is available on the use of epinephrine during breast feeding.
A decision on whether to continue/discontinue breast-feeding or to
continue/discontinue therapy with this medicine should be made taking
into account the benefit of breast-feeding to the child and the benefit
of this medicine therapy to the women. Therefore, nursing mothers
should milk and discard the first mother’s milk following anaesthesia
with lidocaine.

Rare
headache, somnolence
Not known*
facial palsy, paresis, syncope
Eye disorders

Not known*
accommodation disorder, blindness,
diplopia, eye swelling, vision blurred

Cardiac disorders

Rare
palpitations

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Vascular disorders

Rare
haematoma
Not known*
pallor

Respiratory, thoracic and
mediastinal disorder

Not known*
bronchospasm, laryngeal oedema,
respiratory failure, throat tightness,
wheezing

Gastrointestinal disorders

Very common
hypoaesthesia oral
Uncommon
toothache, nausea
Not known*
tongue oedema, vomiting

Skin and subcutaneous
tissue disorders

Rare
haemorrhage subcutaneous
Not known*
dermatitis bullous, dermatitis
contact, hypoaesthesia facial,
pruritus, rash, swelling face

General disorders and
Common
administration site conditions
drug ineffective, pain

Uncommon
injection site swelling, injection site
haematoma
Investigations

Injury, poisoning and
procedural complications

Not known*
allergy test positive, heart rate
increased, heart rate irregular
Uncommon
procedural pain, mouth injury

* data from postmarketing surveillance representing 5 years of observation

c) Description of selected adverse events:
Two types of adverse events are of special clinical interest, but not the
most frequently reported adverse events. The presentation is based mainly
on postmarketing surveillance data.
Nerve disturbances
Nerve disturbances in dentistry may have different reasons, caused by
underlying dental disease, by dental procedure, but also by direct adverse
events of dental local anaesthetics. With an observation frequency of one
event per 10 millions of sold carpules the risk of such disturbances is low.
In the data compilation given above the most frequently reported nerve
disturbance in clinical studies was oral hypoaesthesia (mainly lip numbness).
It should be taken into account that the high number of oral hypoaesthesia
reported in clinical studies may reflect only an individually increased
duration of action of this medicine. During postmarketing surveillance,
cases of facial palsy, hypoaesthesia facial and different adverse eye events
(e.g. diplopia, accommodation disturbances) were identified indicating
possibly anaesthesia related nerve disturbances. All of these adverse
events were reversible.
Hypersensitivity reactions
Hypersensitivity reactions were only rarely identified in the postmarketing
surveillance (6.41 events per 10 millions sold carpules). Mostly the reactions
were non-serious (4.56/10 millions sold carpules), but life-threatening
reactions cannot be fully excluded. The reactions included anaphylactic
reactions/shock, skin reactions and respiratory symptoms.
In the case of suspected hypersensitivity reaction, allergy testing is
recommended including testing of the single components of the medicinal
product.

d) Paediatric population
The observation during postmarketing surveillance does not reveal
differences in the safety profile in children compared with those in adults.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk
balance of the medicinal product. Healthcare professionals are asked to
report any suspected adverse reactions via the Yellow Card Scheme,
Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Acute emergencies from local anaesthetics are generally related to high
plasma levels encountered during therapeutic use or unintended and fast
intravasal administration of local anaesthetics. Symptoms of overdose may
appear either immediately, caused by accidental intravascular injection or
abnormal absorption conditions, e.g. in inflamed or intensive vascularised
tissue, or later, caused by true overdose following an injection of excessive
quantity of anaesthetic solution, and manifest themselves as central
nervous and/or vascular symptoms.
Symptoms probably caused by lidocaine:
Cardiovascular symptoms (SOC Cardiac disorders, Vascular disorders,
Investigations): blood pressure decreased, bradycardia, cardiac arrest,
conduction disorder.
Central nervous symptoms (SOC Psychiatric disorders, Nervous system
disorders, Ear and labyrinth disorders, Gastrointestinal disorders,
Musculoskeletal and connective tissue disorders, Investigations): anxiety,
coma, confusional state, dizziness, dysgeusia, grand mal convulsion,
muscle twitching, nausea, respiratory paralysis, respiratory rate increased,
restlessness, somnolence, tinnitus, tremor, vomiting.
The most dangerous symptoms regarding the outcome of such an event are:
blood pressure decreased, cardiac arrest, conduction disorder, grand mal
convulsion, respiratory paralysis, and somnolence/coma.
Symptoms probably caused by epinephrine (adrenaline):
Pressure symptoms (SOC Vascular disorders, Investigations): blood pressure
systolic increased, blood pressure diastolic increased, venous pressure
increased, pulmonary arterial pressure increased, hypotension.
Cardiac symptoms (SOC Cardiac disorders): bradycardia, tachycardia,
arrhythmia (e.g. atrial tachycardia, atrioventricular block, ventricular
tachycardia, premature ventricular contractions).
These symptoms can result in life threatening situations as well as
pulmonary oedema, cardiac arrest, kidney failure, and metabolic acidosis.
Therapy
If symptoms of overdose arise the application of the local anaesthetic has
to be stopped.
General basic measures:
Diagnostics (respiration, circulation, consciousness), resuscitation and/or
maintenance of the vital functions (respiration and circulation), administration of oxygen, intravenous access.
Special measures:
Hypertension:

Elevation of the upper body, if necessary sublingual
nifedipine.

Convulsions:

Protect patients from concomitant injuries,
if necessary benzodiazepines (e.g. diazepam iv).

Hypotension:

Horizontal position, if necessary intravascular
infusion of a whole electrolyte solution,
vasopressors (e.g. etilefrine iv).

Bradycardia:

Atropine iv.

Anaphylactic shock:

Contact emergency physician, in the meantime
shock positioning, generous infusion of a whole
electrolyte solution, if necessary epinephrine iv,
cortisone iv.

Cardiovascular arrest: Immediate cardiopulmonary resuscitation, contact
emergency physician.

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5 PHARMACOLOGICAL PROPERTIES

Special populations:

6.5 Nature and contents of container

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anaesthetics, local, ATC code N01B B52

Effect of age: Lidocaine has been extensively investigated in elderly
patients. A significantly longer half-life was found for lidocaine in elderly
patients. Reduced clearance was detected only in elderly men, while the
values in females did not differ significantly from younger individuals.
Dose reduction was sometimes suggested for elderly patients (reduction
by approximately 1/3 to 1/2).

Cartridge made of colourless neutral glass I.
Stopper and rubber disc are made of butyl rubber.
Green coloured aluminium cap made of aluminium-iron-silicon-alloy.

Mechanism of action:
This medicine contains lidocaine which is a local anaesthetic of the amide
type for dentistry and leads to a reversible inhibition of the irritability
of vegetative, sensory and motor nerve fibres. The blocking of voltage
dependent Na+ channels on the membrane of the nerve fibre is supposed
to be the mechanism of action of lidocaine.
Epinephrine leads locally to vasoconstriction and reduced blood supply,
whereby the absorption of lidocaine is delayed. The result is a higher
concentration of the local anaesthetic at the site of action over a longer
period, as well as the reduction of systemic adverse side effects.

It is suggested that absorption may be faster and the Cmax higher in children
than in adults, while dependent upon the administered drug, and due to the
larger volume of distribution the Cmax may also be lower and the terminal
half-life longer in children than in adults. For children it seems preferable
to use drugs with higher protein binding and a high hepatic extraction ratio
such as articaine.
Renal and hepatic insufficiency:

Pharmacodynamic effects:
Onset of local anaesthetic effects of this medicine occurs after a short
latency period of 1-3 min with infiltration and after somewhat longer
latency period after injection with nerve block anaesthesia (2 to 4 minutes
after injection). The duration of complete anaesthesia with this medicine
in pulpal anaesthesia is 30 to 60 minutes, and in soft-tissue anaesthesia
120 to 180 minutes.

The elimination half-life of lidocaine following an intravenous bolus
injection is typically 1.5 to 2.0 hours. Because of the rapid rate at which
lidocaine is metabolized, any condition that affects liver function may alter
lidocaine kinetics. The half-life may be doubled or more in patients with
liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but
may increase the accumulation of metabolites.

Clinical efficacy and safety:
Success rates of anaesthesia with this medicine differ, depending on the
kind of anaesthesia and the factors already mentioned before. In general,
success rates of about 90% or higher may be expected after single use if
the drug is administered as indicated. The inferior alveolar nerve block
has the greatest failure rate. Repeated or supplementary injections may
be necessary in the event of failure or in the event of prolonged dental
procedures and surgery. Special conditions, e.g. acute irreversible pulpitis
of mandibular molars, may require special or alternative anaesthetic
techniques. Articaine 4% with epinephrine may provide better clinical
efficacy in such cases as reported by different authors. this medicine is
usually tolerated well however, adverse reactions cannot be fully excluded
(see section 4.8), in the event of overdose in particular (see section 4.9).

5.3 Preclinical safety data

Paediatric population:
The use of this medicine in paediatric population is considered for routine
treatment. Dosages in paediatric population should be reduced considering
age, body weight, physical condition and the magnitude of the treatment
(see section 4.2), together with complex measures to prevent painful
experience and to reduce anxiety, including sedation.
Since paediatric patients suffer relatively often traumatic injury to their still
(residual) anaesthetized soft tissue following local anaesthesia administration in the dental office (reportedly 13%), local anaesthesia providing the
appropriate duration of efficacy should be used.
5.2 Pharmacokinetic properties
Absorption:
Lidocaine is rapidly and extensively absorbed. The maximum plasma
level of lidocaine from intraoral injection is achieved approximately after
10-20 minutes.
Distribution:
Lidocaine is bound up to 60 to 80 % in the serum to plasma proteins.
Lidocaine is widely distributed within the organism. The elimination half-life
is 1.5 to 2 hours.
Biotransformation and elimination:
Lidocaine is largely metabolised in the liver and any alteration in liver
function or hepatic blood flow can have a significant effect on its
pharmacokinetics and dosage requirements. Metabolism in the liver
is rapid and about 90 % of the given dose is dealkylated to form monoethylglycinexylidide and glycinexylidide. Less than 10 % is excreted
unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy2,6-dimethylaniline.
Lidocaine crosses the blood-brain and placental barriers.
Epinephrine is rapidly catabolized in the liver and other tissues. The metabolites are excreted renally.

There is evidence that 2,6-xylidine, a metabolic product arising from
lidocaine in the rat, and possibly also in man, can have mutagenic effects.
This evidence is obtained from in-vitro tests in which the said metabolite
was used at very high, almost toxic concentrations. There is no reason
to believe at this time that the parent substance, lidocaine, is itself also
mutagenic.
A carcinogenicity study of transplacental exposure and postnatal treatment
of animals for two years with 2,6-xylidine in rats demonstrated malignant
and benign tumors predominantly in the nasal cavities (ethmoturbinalia)
by means of a highly sensitive test system (transplacental exposure and
postnatal treatment of animals for two years with very high doses). It does
not seem totally unlikely that these findings will be relevant to humans.
For this reason high doses of this medicine (lidocaine) should not be
administered over longer periods.
While supratherapeutic doses of lidocaine and epinephrine administered
under in vitro or in vivo experimental conditions to laboratory animals
may affect fertilization and foetal development, harmful or other effects
on female or male fertility are not expected based on animal studies at
therapeutic doses of lidocaine and epinephrine (see section 4.6).
Environmental Risk Assessment (ERA):
Environmental Risk Assessment does not reveal substantial risk.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Anhydrous sodium sulphite (E221)
Sodium chloride
Hydrochloric acid 14% (for pH adjustment)
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be
mixed with other medicinal products.
6.3 Shelf-life
18 months
6.4 Special precautions for storage
Do not store above 25° C.
Do not refrigerate.
Store in the original package (tin) in order to protect from light.

Tin with 50 cartridges of 1.7 ml each.
6.6 Special precautions for disposal and other handling
The product should be inspected visually for particulate matter, discoloration
or damage of container prior to administration. The product should not be
used if such defects are observed.
The product is for single use only. Any unused product should be disposed
immediately after first use in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
3M Health Care Limited
3M House, Morley Street
Loughborough, Leicestershire LE 11 1EP, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 00068/0408
9 DATE OF FIRST AUTHORISATION/
RENEWAL OF THE AUTHORISATION
02/10/2014
10 DATE OF REVISION OF THE TEXT
03/12/2014

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medicine if you are pregnant, think you may be pregnant or you are planning
to have a baby.
Breast-feeding
If you are breast-feeding ask your doctor or dentist for advice before taking
this medicine.
• Following anaesthesia with this medicine nursing mothers should milk and
discard this first milk before resuming breast-feeding.
Driving and using machines
Although this medicine should not impair your ability to drive, the dentist
should assess you, for your individual safety, after treatment and you should
not leave the dental office until 30 minutes after the injection.
Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml contains
sodium sulfite
Anhydrous sodium sulfite (one of the ingredients of this medicine) may rarely
cause severe hypersensitivity reactions including anaphylactic symptoms and
bronchospasm in susceptible people, especially those with a history of asthma
or allergy.
The medicinal product contains less than 1 mmol sodium (23 mg) per 1.7 ml,
i.e. essential “sodium-free”.
3. HOW TO USE XYLESTESIN™ WITH ADRENALINE 20 MG/ML +
12.5 MICROGRAMS/ML
The medicinal product is only used by a dentist
Dosage
The dentist will choose the dose of this medicine that is appropriate for you.
In any case your dentist will use the smallest possible volume of solution
which will lead to an effective anaesthesia. For uncomplicated procedures
your dentist will administer 0.5 to 1.7 ml solution for injection.
Use in adults:
The maximum recommended dosage for healthy adults is 0.350 ml of solution
per kg/body weight Due to the maximum dose of adrenaline (epinephrine)
(0.2 mg) 16 ml solution should not be exceeded. A lower dosage range is
recommended in case of angina pectoris, reduced general condition, older
patients, severe impaired renal and liver function and arteriosclerosis.
Use in children and adolescents:
The dentist has to exercise special care when treating children below 4 years.
The quantity which the dentist has to inject should be determined by the age
and weight of the child and the magnitude of the operation. The dentist will
select the anaesthesia technique carefully to avoid painful injection. During
the treatment the dentist will monitor the behavior of the child carefully.
The average dose to be used is in the range of 1 ml to 1.5 ml of this medicine
per session. The maximum recommended dosage of 0.250 ml of solution per
kg body weight should not be exceeded.
Method and route of administration:
The medicinal product is for dental use only. This medicine will be administered
to you as an injection into your oral cavity by the dentist.
Generally treatment with this medicine is a single treatment.
If you have any further questions on the use of this product, ask your doctor,
dentist or pharmacist.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Severe Allergic Reactions (Frequency not known)
If you notice one of the following signs within a day of the dental procedure, tell
your dentist immediately as they may be the signs of a severe allergic reaction:
Swelling of your face, lips, tongue or throat.
Difficulty breathing or wheezing due to throat tightness, bronchospasm;
respiratory failure cannot be excluded
Itching, rash, inflammation of skin or mucosa
Hypersensitivity testing is strongly recommended to avoid such events in the
future.
Nerve Disturbances (Frequency not known)
If you feel e.g. numbness, tingling, stinging, taste problems or double vision
within one day of the dental procedure please contact your dentist. Nerve
disturbances can persist for longer time, but in most cases these symptoms
disappear within a few months. The signs may include:
- Face numbness, facial paralysis
- Eye disorders, e.g. double vision, blurred vision, eye swelling, transient
blindness, disturbed focusing
Other side effects
The following adverse events were recorded in clinical studies or during postmarketing surveillance.

Very common (may affect more than 1 in 10 people)
- Prolonged numbness of the mouth due to the anaesthesic lasting longer
than expected
Common (may affect up to 1 in 10 people)
- Insufficient anaesthesia which results in some pain during the procedure
Uncommon (may affect up to 1 in 100 people)
- Dizziness, feeling sick
- Infections of the mouth area (e.g. oral herpes)
- Injury to mouth caused by accidental biting while the mouth is still numb
- Bruise or swelling at injection site
- Toothache
Rare (may affect up to 1 in 1,000 people)
- Headache
- Drowsiness
- Abnormal heartbeat
- Bruise, bleeding beneath the skin
Frequency not known
- Fainting
- Confusion, pallor, vomiting, increased or irregular heart rate. These may
also be signs before fainting
Additional side effects in children and adolescents
Neither data from clinical studies nor postmarketing observations revealed
differences in safety between adults and children and adolescents.
Reporting of side effects
If you get any side effects, talk to your doctor, dentist or pharmacist. This
includes any possible side effects not listed in this leaflet. You can also report
side effects directly via the internet at www.mhra.gov.uk/yellowcard. Alternatively you can call Freephone 0808 100 3352 (available from 10 a.m. to 2 p.m.
Mondays to Fridays) or fill in a paper form available from your local pharmacy.
By reporting side effects you can help provide more information on the safety
of this medicine.
5. HOW TO STORE XYLESTESIN™ WITH ADRENALINE 20 MG/ML +
12.5 MICROGRAMS/ML
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the bottom
of the tin and the cartridge after EXP. The expiry date refers to the last day of
that month.
Do not store above 25° C. Do not refrigerate. Store in the original package
(tin) in order to protect from light.
Do not use this medicine if you notice particulate matter, discoloration or
damage of container prior to administration.
The product is for single use only. Any unused product should be discarded
immediately after first use.
Do not throw away any medicines via wastewater or household waste.
Ask your pharmacist how to throw away medicines you no longer use. These
measures will help to protect the environment.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml
contains
The active substances are Lidocaine hydrochloride and Adrenaline (epinephrine).
- 1 ml solution for injection contains 20 mg Lidocaine hydrochloride and
12.5 micrograms Adrenaline (epinephrine).
- 1 cartridge with 1.7 ml solution for injection contains 34 mg Lidocaine
hydrochloride and 21.25 micrograms Adrenaline (epinephrine).
- The other ingredients are anhydrous sodium sulphite (E221), sodium
chloride, and water for injections as well as hydrochloric acid 14% for
adjusting the pH-value.
What Xylestesin™ with Adrenaline 20 mg/ml + 12.5 micrograms/ml looks
like and contents of the pack
Solution for injection
The solution is a clear, not opalescent, colourless liquid
Tin with 50 cartridges of 1.7 ml each
Marketing Authorisation Holder
3M Health Care Limited
3M House, Morley Street
Loughborough, Leicestershire LE 11 1EP, UK
Manufacturer
3M Deutschland GmbH
Carl-Schurz-Strasse 1, D-41453 Neuss, Germany
This leaflet was last approved in
October 2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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